Luigi Longobardo Università di Napoli Federico II Dipartimento di Chimica Organica e Biochimica studio: 0Mb-14; Lab: 0Mb-06 Via Cinthia 4 - 80126 - Napoli, Italy Tel: +39081674115 Fax: +39081674102
Abstract: The general synthesis of a new class of non-natural diamino acids, 2-amino-3-[(2'-aminoalkyl)seleno]propanoic acids, or Se-(aminoalkyl)selenocysteines, is reported. Under the conditions devised, enantiopure N-Boc-protected beta-L-iodoamines, which are readily generated from proteinogenic alpha-amino acids, were treated with the selenolate anion obtained from NaBH4 splitting of the Se-Se bond in commercial L-selenocystine. The Se-alkylation products were enantiomerically pure and the reaction is high yielding (92-98%), without any detectable traces of accompanying by-products.
Abstract: A procedure for the synthesis of enantiopure beta(3)-amino acids from proteinogenic alpha-amino acids, developed by our group a few years ago, has been modified to enable the production of C-2 fully deuterated, C-protected beta(3)-amino acids and, even more important, the synthesis of valuable deuterium labelled N(Boc)-protected chiral synthons, such as 2-aminoalcohols, 2-aminoiodides, and beta(3)-amino nitriles.
Abstract: he general synthesis of a new class of non-natural diamino acids, 2-amino-3-[ (2'-aminoalkyl)thio]propanoic acids or S(aminoalkyl)cysteines, is reported. Under the conditions devised, enantiopure N-Boc-protected beta-iodoamines, readily generated from proteinogenic a-amino acids, are treated with L-cysteine ethyl ester hydrochloride, using Cs2CO3 as a base. The S-alkylation products, obtained in high yields (96-98%) and without any detectable traces of accompanying byproducts, are hydrolysed to yield the free carboxyl group. An orthogonal protection is then introduced on the free amino group by treatment with Fmoc-OSu under standard conditions. The inclusion of one of these orthogonally protected diamino acids in a solid-phase growing pentapeptide is also reported.
Abstract: BACKGROUND: Celiac disease is a widely prevalent enteropathy caused by intolerance to gliadin, one of the gluten proteins. We developed two methods for the analysis of gliadin levels. Both methods use flow cytometry and rat antibodies against a 16-residue peptide of gliadin. The peptide is common to the alpha-, beta-, gamma-, and omega-gliadins. METHODS: In the one-site assay, the antigen (gliadin standard or food extract) was adsorbed on 3-mum latex particles. Sensitized particles were then incubated, in this order, with rat anti-gliadin peptide antibodies and anti-rat immunoglobulin G antibodies labeled with fluorescein isothiocyanate. In the two-site assay, the antigen was trapped on the latex particles by rat anti-gliadin antibodies and then measured by the same antibodies labeled with fluorescein. RESULTS: Detection limits were 1 ng/ml for the one-site assay and 10 pg/ml for the two-site assay. The two-site assay displayed gliadin at concentrations above the limit proposed by the Codex Alimentarius in 2 of 40 gluten-free products. CONCLUSION: There is a growing concern that gliadin, even when present in gluten-free foods within the limit fixed by the Codex Alimentarius, over the long term may become toxic to patients with celiac disease. The techniques described in this study provide an opportunity to further decrease the acceptable limit of gliadin in gluten-free foods.
Abstract: A peptidomics approach was developed to identify transglutaminase-susceptible Q residues within a pepsin-trypsin gliadin digest. Based on tagging with a monodansylcadaverine fluorescent probe, six alpha/beta-, gamma-gliadin, and low molecular weight glutenin peptides were identified by nanospray tandem mass spectrometry. In functioning as an acyl acceptor, tissue transglutaminase was able to form complexes with the glutamine-rich gliadin peptides, whereas by lowering pH, the peptides were deamidated by transglutaminase at the same Q residues, which were previously transamidated. The main common feature shared by the peptides was the consensus sequence Q-X-P. Our findings offer relevant information for the understanding of how dietary peptides interact with the host organism in celiac disease.
Abstract: Developing seeds from Triticum aestivum (wheat) cultivars were collected after flowering and analysed for puroindoline a and b gene expression by Real Time RT-PCR. Mature seeds were investigated for the presence and the amount of starch-associated puroindoline a and b proteins by flow cytometry. Puroindoline a gene and protein were found to have a predominant role in controlling wheat kernel hardness.
Abstract: An efficient approach for the synthesis of cyclic peptides containing unnatural thioether side-chain bridges, based on the use of (2 S)-9-fluorenylmethyl-2[(tert-butoxycarbonyl)amino]-4-iodobutanoate and its homologue 5-iodopentanoate, derived from Boc-L-Asp-OFm and Boc-L-Glu-OFm, respectively, is reported. The synthesis was performed by a tandem combination of solid-phase peptide synthesis and microwave-assisted cyclization strategy.
Abstract: Two analogues of bovine beta-casomorphin-7 and beta-casomorphin-5 containing a beta-homo phenylalanine in substitution of the phenylalanine in position 3 were synthesised and tested for their mu-opioid receptor affinity. The modification enhanced the mu receptor affinity 5-fold in the case of modified beta-CM-7 and 2-fold for modified beta-CM-5 when compared to the natural peptides.
Abstract: The stereoselectivity of the Lewis acid induced acylation of open-chain silyl enol ethers by chiral orthoesters is strongly affected by the C = C bond configuration: both Z and E silyl enol ethers are acylated in good isolated yields, but the Z isomers give rise to a 1:1 ratio of diastereoisomeric monoprotected 1,3-diketones, while excellent stereoselectivities are obtained with E enols.
